Open figure viewer
Abstract
Introduction: Recurrent urinary tract infections (rUTIs) are prevalent among women and substantially impair quality of life, underscoring the need for effective and safe preventive treatments. This study evaluated the efficacy, safety, and bacterial resistance rates of methenamine hippurate (MH) versus low-dose nitrofurantoin (NFT) for rUTI prevention in women. Methods: We conducted a retrospective propensity score-matched cohort study involving female rUTI patients from our urology clinic between June 2021 and February 2024. After 1:1 matching, 50 patients each constituted the MH group and the low-dose NFT group. The treatment and follow-up period was 12 months, with assessments at 3, 6, and 12 months. A non-inferiority margin of Δ = 0.5 episodes per person-year was defined. The primary endpoint was the 12-month symptomatic UTI recurrence rate. Secondary outcomes included urine culture positivity, pathogen profile, antibiotic resistance, asymptomatic bacteriuria, IPSS, SF-36, direct costs, compliance, and adverse events. Results: After propensity score matching, baseline characteristics were balanced. The 12-month recurrence rates were 18.00% for MH and 20.00% for NFT, confirming non-inferiority (p = 0.765). Urine culture positivity and pathogen profiles did not differ significantly. MH showed no detectable resistance versus 28.57% in NFT (p = 0.022) and lower asymptomatic bacteriuria (8.00% vs. 22.00%; p = 0.037). Compliance was similar. MH resulted in significantly improved IPSS and SF-36 scores (p < 0.001). Although drug costs were higher with MH, total management costs were lower (p < 0.001), with fewer adverse events (p < 0.05). Conclusion: MH demonstrates non-inferiority to low-dose NFT for preventing rUTIs in women, with reduced resistance, adverse events, and asymptomatic bacteriuria. Despite higher drug cost, its superior long-term benefit supports its use as an alternative in NFT-intolerant or high-risk patients.
Journal Section:
Research Article
References
1.
Expert Panel on Urological Imaging
, Venkatesan
AM
, Oto
A
, Allen
BC
, Akin
O
, Alexander
LF
, et al. ACR appropriateness criteria® recurrent lower urinary tract infections in females
. J Am Coll Radiol
. 2020
;17
(11S
):S487
–96
. 2.
Cornelius
SA
, Basu
U
, Zimmern
PE
, De Nisco
NJ
. Overcoming challenges in the management of recurrent urinary tract infections
. Expert Rev Anti Infect Ther
. 2024
;22
(12
):1157
–69
. 3.
Liao
W-J
, Jiang
Y-H
, Jhang
J-F
, Chen
S-F
, Lee
YK
, Lee
C-L
, et al. Pathophysiology and potential treatment modalities in women with recurrent urinary tract infection
. Tzu Chi Med J
. 2025
;37
(2
):117
–24
. 4.
Scott
VCS
, Thum
LW
, Sadun
T
, Markowitz
M
, Maliski
SL
, Ackerman
AL
, et al. Fear and frustration among women with recurrent urinary tract infections: findings from patient focus groups
. J Urol
. 2021
;206
(3
):688
–95
. 5.
Iossa
V
, Masciovecchio
S
, Clemente
GB
, Chiaramonti
F
, Ciotta
C
, Pandolfo
SD
, et al. Comparison of increased hydration, D-mannose, and antibiotic prophylaxis for recurrent urinary tract infection prevention in premenopausal women: a three-arm randomized-controlled study
. Int Urol Nephrol
. 2026
;58
(3
):881
–87
. 6.
Bint Karim
S
, Mustafa
G
, Jabeen
A
, Azam
P
, Nawaz Minhas
I
, Zafar
S
. The role of hormonal changes in recurrent urinary tract infections among postmenopausal women. A clinical perspective study
. Pak J Med Health Sci
. 2023
;17
(9
):50
–2
. 7.
Ochoa
DC
, Healy
R
. Intravesical agents for prevention of recurrent urinary tract infections
. Eur Urol Focus
. 2024
;10
(5
):726
–30
. 8.
Gutiérrez-Aceves
JA
, Avalos-Salgado
FA
, Gamez-Nava
JI
, Gonzalez-Lopez
L
, González-Vázquez
SA
, Arellano-Cervantes
R
, et al. Nitrofurantoin as an add-on to conventional prophylaxis for the treatment of urinary tract infections in kidney recipients: a prospective cohort study
. J Clin Med
. 2024
;13
(17
):5218
. 9.
Kale
S
, Somani
BK
. The resurgence of methenamine hippurate in the prevention of recurrent UTIs in women-a systematic review
. Curr Opin Urol
. 2023
;33
(6
):488
–96
. 10.
Brumfitt
W
, Cooper
J
, Hamilton-Miller
JMT
. Prevention of recurrent urinary infections in women: a comparative trial between nitrofurantoin and methenamine hippurate
. J Urol
. 1981
;126
(1
):71
–4
. 11.
Ten Doesschate
T
, Hendriks
K
, van Werkhoven
CH
, van der Hout
EC
, Platteel
TN
, Groenewegen
IAM
, et al. Nitrofurantoin 100 mg versus 50 mg prophylaxis for urinary tract infections, a cohort study
. Clin Microbiol Infect
. 2022
;28
(2
):248
–54
. 12.
Watson
JR
, Newland
JG
. Recurrent urinary tract infection prevention: progress and challenges
. Pediatrics
. 2024
;154
(6
):e2024068728
. 13.
Wu
S
, Hu
FP
, Jiang
XF
, Zhu
DM
, Liu
Y
, Qin
Q
, et al. Bacterial resistance surveillance in Shanghai’s third-level hospitals in 2019
. Chin J Infect Chemotherap
. 2021
;21
(1
):1
–10
. 14.
Mazumder
MM
, Uddin Noman
M
, Hasan
AKMT
, Ahammod
T
, Abdullah Rafique
A
, Rahman
M
. Bacteriological profile and antibiotic sensitivity pattern of urinary tract infection
. East West Med Coll J
. 2025
;13
(1
):23
–7
. 15.
Madani
Y
, Mann
B
. Nitrofurantoin-induced lung disease and prophylaxis of urinary tract infections
. Prim Care Respir J
. 2012
;21
(3
):337
–41
. 16.
Huang
J
, Zhang
J
, Sun
C
, Yang
R
, Sheng
M
, Hu
J
, et al. Adjuvant role of Salvia miltiorrhiza bunge in cancer chemotherapy: a review of its bioactive components, health-promotion effect and mechanisms
. J Ethnopharmacol
. 2024
;318
(Pt B
):117022
. 17.
Mikkelsen
LF
, Rubak
S
. Reversible lung fibrosis in a 6-year-old girl after long term nitrofurantoin treatment
. BMC Pulm Med
. 2020
;20
(1
):313
. 18.
Vaughn
VM
, Gupta
A
, Petty
LA
, Malani
AN
, Osterholzer
D
, Patel
PK
, et al. A statewide quality initiative to reduce unnecessary antibiotic treatment of asymptomatic bacteriuria
. JAMA Intern Med
. 2023
;183
(9
):933
–41
. 19.
Gleckman
R
, Alvarez
S
, Joubert
DW
, Matthews
SJ
. Drug therapy reviews: methenamine mandelate and methenamine hippurate
. Am J Hosp Pharm
. 1979
;36
(11
):1509
–12
. 20.
Petersen
S
. Long‐term prophylaxis with methenamine hippurate in girls with recurrent urinary tract infections
. Acta Paediatr
. 1978
;67
(5
):597
–9
. 21.
Botros
C
, Lozo
S
, Iyer
S
, Warren
A
, Goldberg
R
, Tomezsko
J
, et al. Methenamine hippurate compared with trimethoprim for the prevention of recurrent urinary tract infections: a randomized clinical trial
. Int Urogynecol J
. 2022
;33
(3
):571
–80
. 22.
Hernández-Sánchez
JE
, Szczesnieski
JJ
, Padilla-Fernández
B-Y
, González-Enguita
C
, Flores-Fraile
J
, Lorenzo-Gómez
MF
. Evaluation and analysis of costs associated with prophylaxis of recurrent urinary tract infections (RUTIs) in women
. Microorganisms
. 2025
;13
(2
):393
. 23.
Kamalkar
HG
, Halwar
KM
, Pawar
KS
, Dange
MD
, Virkar
MP
, Kulkarni
K
. Efficacy of nitrofurantoin in treating urinary tract infections
. Int J Adv Res Sci Commun Technol
. 2024
:119
–25
. 24.
Harding
C
, Mossop
H
, Homer
T
, Chadwick
T
, King
W
, Carnell
S
, et al. Alternative to prophylactic antibiotics for the treatment of recurrent urinary tract infections in women: multicentre, open label, randomised, non-inferiority trial
. BMJ
. 2022
;376
:e068229
. 25.
National Institute for Health and Care Excellence: Clinical Guidelines
. Urinary tract infection (recurrent): antimicrobial prescribing
. London
: National Institute for Health and Care Excellence (NICE)
; 2024
.26.
Anger
J
, Lee
U
, Ackerman
AL
, Chou
R
, Chughtai
B
, Clemens
JQ
, et al. Recurrent uncomplicated urinary tract infections in women: AUA/CUA/SUFU guideline
. J Urol
. 2019
;202
(2
):282
–9
. 27.
Nicolle
LE
, Bradley
S
, Colgan
R
, Rice
JC
, Schaeffer
A
, Hooton
TM
, et al. Infectious diseases society of America guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults
. Clin Infect Dis
. 2005
;40
(5
):643
–54
. 28.
Okamura
K
, Nojiri
Y
, Osuga
Y
, Tange
C
. Psychometric analysis of international prostate symptom score for female lower urinary tract symptoms
. Urology
. 2009
;73
(6
):1199
–202
. 29.
Choi
EPH
, Lam
CLK
, Chin
W-Y
. Validation of the international prostate symptom score in Chinese males and females with lower urinary tract symptoms
. Health Qual Life Outcomes
. 2014
;12
(1
):1
. 30.
Hsiao
S-M
, Lin
H-H
, Kuo
H-C
. International prostate symptom score for assessing lower urinary tract dysfunction in women
. Int Urogynecol J
. 2013
;24
(2
):263
–7
. 31.
Zhou
B
, Chen
K
, Wang
JF
, Wu
YY
, Zheng
WJ
, Wang
H
. Reliability and validity of a Short-Form Health Survey Scale (SF-36), Chinese version used in an elderly population of Zhejiang province in China
. Zhonghua Liu Xing Bing Xue Za Zhi
. 2008
;29
(12
):1193
–8
. 32.
Osterberg
L
, Blaschke
T
. Adherence to medication
. N Engl J Med
. 2005
;353
(5
):487
–97
. 33.
Freites-Martinez
A
, Santana
N
, Arias-Santiago
S
, Viera
A
. Using the common terminology criteria for adverse events (CTCAE - Version 5.0) to evaluate the severity of adverse events of anticancer therapies
. Actas Dermosifiliogr
. 2021
;112
(1
):90
–2
. 34.
Turcu
FL
, Vacaroiu
IA
, Balcangiu-Stroescu
AE
, Mitrea
AR
, Miricescu
D
, Balan
DG
, et al. Recurrent urinary tract infections in female patients—A clinical review
. J Mind Med Sci
. 2025
;12
(1
):5
. 35.
Saul
H
, Deeney
B
, Cassidy
S
, Kwint
J
, Harding
C
. Methenamine is as effective as antibiotics at preventing urinary tract infections
. BMJ
. 2023
;380
:72
. 36.
Lazarus
JE
, Gupta
K
. Recurrent UTI in women–risk factors and management
. Infect Dis Clin North Am
. 2024
;38
(2
):325
–41
. 37.
Chen
L
, Kumar
S
, Wu
H
. A review of current antibiotic resistance and promising antibiotics with novel modes of action to combat antibiotic resistance
. Arch Microbiol
. 2023
;205
(11
):356
. 38.
Khurshid
F
, Aziz
H
, Zain
M
, Arshad
F
, Mughal
M
, Ghazanfar
T
. Prevalence of antibiotic resistance in patients with urinary tract infections
. J Shifa Tameer-e-Millat Univ
. 2024
;7
(1
):52
–60
. 39.
Kranz
J
, Bartoletti
R
, Bruyère
F
, Cai
T
, Geerlings
S
, Köves
B
, et al. European association of urology guidelines on urological infections: summary of the 2024 guidelines
. Eur Urol
. 2024
;86
(1
):27
–41
. 40.
Harding
C
, Chadwick
T
, Homer
T
, Lecouturier
J
, Mossop
H
, Carnell
S
, et al. Methenamine hippurate compared with antibiotic prophylaxis to prevent recurrent urinary tract infections in women: the ALTAR non-inferiority RCT
. Health Technol Assess
. 2022
;26
(23
):1
–172
. 41.
Schiøtz
HA
, Guttu
K
. Value of urinary prophylaxis with methenamine in gynecologic surgery
. Acta Obstet Gynecol Scand
. 2002
;81
(8
):743
–6
. 42.
Wullt
B
, Svanborg
C
. Deliberate establishment of asymptomatic bacteriuria—A novel strategy to prevent recurrent UTI
. Pathogens
. 2016
;5
(3
):52
. 43.
Stefanović
T
, Stojković
E
. Use of antibiotic therapy for recurrent urinary tract infections caused by Escherichia coli
. Opšta medicina
. 2024
;30
(3–4
):137
–43
. 44.
Clarke
C
, Harding
C
. Methenamine as prophylaxis for recurrent urinary tract infections: an overview of the ALTAR trial
. Obstet Gynaecol Reprod Med
. 2022
;32
(12
):289
–90
. 45.
Lutchka
J
, Vercnocke
J
, Fisher
E
, Radoiu
C
, Jeberaeel
J
, Lucas
S
, et al. Treatment of chronic post-radiation cystitis with trans-urethral amniotic bladder therapy appears durable at 9 months: a clinical study
. Urologia
. 2024
;91
(3
):623
–7
. 46.
Aghajanyan
I
, Allen
S
. Positive response to thermobalancing therapy enabled by therapeutic device in men with non-malignant prostate diseases: BPH and chronic prostatitis
. Diseases
. 2016
;4
(2
):18
. 47.
Carrión-López
P
, Martínez-Ruiz
J
, Giménez-Bachs
JM
, Fernández-Anguita
PJ
, Díaz de Mera-Sánchez Migallón
I
, Legido-Gómez
O
, et al. Cost-effectiveness of a sublingual bacterial vaccine for the prophylaxis of recurrent urinary tract infections
. Urol Int
. 2022
;106
(7
):730
–6
. 48.
Davidson
SM
, Brown
JN
, Nance
CB
, Townsend
ML
. Use of methenamine for urinary tract infection prophylaxis: systematic review of recent evidence
. Int Urogynecol J
. 2024
;35
(3
):483
–9
. © 2026 S. Karger AG, Basel
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
2026
You do not currently have access to this content.
